Abstract
Alzheimer’s disease (AD) is characterized by a large number of amyloid-β (Aβ) deposits in the brain. Therefore, inhibiting Aβ aggregation or destabilizing preformed aggregates could be a promising therapeutic target for halting/slowing the progression of AD. Chitosan oligosaccharides (COS) have previously been reported to exhibit antioxidant and neuroprotective effects. Recent study shows that COS could markedly decrease oligomeric Aβ-induced neurotoxicity and oxidative stress in rat hippocampal neurons. However, the potential mechanism that COS reduce Aβ-mediated neurotoxicity remains unclear. In the present study, our findings from circular dichroism spectroscopy, transmission electron microscope and thioflavin T fluorescence assay suggested that COS act as an inhibitor of Aβ aggregation and this effect shows dose-dependency. Moreover, data from thioflavin T assay indicated that COS could significantly inhibit fibrils formation and disrupt preformed fibrils in a dose-dependent manner. Furthermore, the addition of COS attenuated Aβ1-42-induced neurotoxicity in rat cortical neurons. Taken together, our results demonstrated for the first time that COS could inhibit Aβ1-42 fibrils formation and disaggregate preformed fibrils, suggesting that COS may have anti-Aβ fibrillogenesis and fibril-destabilizing properties. These findings highlight the potential role of COS as novel therapeutic agents for the prevention and treatment of AD.
Highlights
Alzheimer’s disease (AD) is a progressive, age-related neurodegenerative disorder, characterized by the deposition of amyloid β (Aβ) forming senile plaques (SPs), intracellular neurofibrillary tangles (NFTs) and neuronal loss in the brain of AD patients [1,2]
Circular dichroism (CD) spectroscopy provides a general indicator for the increase in β-structure content that accompanies the aggregation of the Aβ peptide [14]
To investigate the structural changes of the peptide, CD spectroscopy in the far UV region (190–240 nm) was applied to detect the changes in secondary structure of Aβ1-42 (Aβ42) alone or peptides coincubated with Chitosan oligosaccharides (COS) for 48 h respectively
Summary
Alzheimer’s disease (AD) is a progressive, age-related neurodegenerative disorder, characterized by the deposition of amyloid β (Aβ) forming senile plaques (SPs), intracellular neurofibrillary tangles (NFTs) and neuronal loss in the brain of AD patients [1,2]. Given the growing prevalence and poor prognosis of AD, there is an urgent need to develop novel, effective therapeutic approaches that ameliorating the disease symptoms and slowing down or inhibiting the underlying neurodegenerative process. Our recent study suggested that COS could markedly attenuate oligomeric Aβ1-42-induced neurotoxicity via repression of oxidative stress and blocking Aβ-mediated phosphorylation of c-Jun N-terminal kinase [13]. We investigated the potential effect of COS on preventing monomeric Aβ aggregation, dissembling preformed fibrils and Aβ-mediated neurotoxicity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
